Gene expression and cancer

Question 1

What are proto-oncogenes?

Answer 1

• normal genes that stimulate DNA replication
  and cell division when activated – occurs when
  growth factors bind to protein receptors on the
  cell-surface membrane

Question 2

What happened when proto-oncogenes are mutated?

Answer 2

• becomes permanently activated, this results in a protein forming that speeds up the rate of cell
  division too much, leading to uncontrolled cell division and a tumour growing
• Hypomethylation (reduced methylation of DNA) has been found to occur in oncogenes, leading to their activation and the formation of tumour

Question 3

What are tumour suppressor genes?

Answer 3

• produce a protein that maintains a slow rate of cell division, repairs DNA errors and triggers apoptosis (programmed cell death)

Question 4

What happens if a tumour suppressor gene mutates?

Answer 4

• change the amino acid sequence of a protein, which means it may not be able to slow down the rate of cell division, increasing the risk of uncontrolled cell division and a tumour growing
• Hypermethylation of DNA in the promoter region of a TSG prevents transcription - the gene is ‘switched off’ e.g. occurs in BRCA1 TSG leading to breast cancer

Question 5

why it is critical that consideration is given to the type of drugs given, and their dosage?

Answer 5

• The drugs must only target cancer cells, as this therapy has the potential to damage healthy cells

Question 6

The KRAS gene codes for a protein called K-Ras. The protein relays signals from outside a cell to a cell’s nucleus, stimulating cell division. An alteration in the KRAS gene produces an oncogene which can cause a tumour to develop. Suggest and explain how an alteration in the KRAS gene can cause a tumour to develop.

Answer 6

• Mutation in KRAS gene OR change in base sequence of KRAS gene;
• change in (signalling) protein OR more (signalling) protein/K-Ras produced;
• results in rapid/uncontrolled cell division. (Reject: any idea that ‘no protein’ or a ‘non-functional’ protein is produced)

Question 7

Define what is meant by epigenetics.

Answer 7

• Heritable changes in gene function;
• without changes to the base sequence of DNA

Question 8

Give one way in which benign tumours differ from malignant tumours

Answer 8

• Cells of benign tumours cannot spread to other parts of the body / metastasise
• OR cells of benign tumours cannot invade neighbouring tissues

Question 9

Explain how increased methylation could lead to
cancer.

Answer 9

• Methyl groups added to (both copies of) a tumour suppressor gene;
• transcription of tumour suppressor genes is inhibited;
• leading to uncontrolled cell division

Question 10

How does the amount of methylation of tumour suppressor genes and oncogenes impact the risk of cancer…and what implications would this have for the design of cancer treatments.

Answer 10

1. Methylation of an oncogene will inhibit transcription of this gene. This could prevent
   uncontrolled cell division and tumour formation. A drug that increases methylation of oncogenes could be used to treat cancer by inhibiting transcription of these genes.
2. Methyl groups added to a normal tumour suppressor gene will inhibit transcription of
   this gene. This could lead to uncontrolled cell division and tumour formation. A drug that decreases methylation of tumour suppressor genes could be used to treat cancer by increasing transcription of these genes